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BMC Neurosci. 2007 Mar 13;8:20.

A comparative genomics approach to identifying the plasticity transcriptome.

Author information

1
Department of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA. andreas.pfenning@duke.edu <andreas.pfenning@duke.edu>

Abstract

BACKGROUND:

Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function.

RESULTS:

We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors.

CONCLUSION:

These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties.

PMID:
17355637
PMCID:
PMC1831778
DOI:
10.1186/1471-2202-8-20
[Indexed for MEDLINE]
Free PMC Article

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